Oxaalkanoate anti-ulcer compounds

ABSTRACT

Certain oxaalkanoate zwitterionic surfactant-type compounds and their esters are not only excellent detergents, but also provide superior oral therapy for ulceration of the gastric mucosa. The oxaalkanoate zwitterionic compounds are especially preferred in the management of both gastric and duodenal ulcers.

TECHNICAL FIELD

The present invention relates to novel surfactant compounds which areuseful for preventing or relieving ulceration of the gastric mucosa.More specifically, the n-C₁₄ - through n-C₂₂ -oxaalkanoate compoundsdisclosed hereinafter have now been found to be unusually effective inthe management of "peptic" ulcers.

The co-pending application of Laughlin and Fu, Ser. No. 57,922, filedJuly 16, 1979, which has issued as U.S. Pat. No. 4,263,281 on Apr. 21,1981, entitled OXAALKANOATE ANTI-ULCER COMPOSITION, discloses the use ofoxaalkanoate zwitterionic compounds, including those of the presentinvention, to treat ulcers, including gastric or duodenal ulcers such asthose related to stress, including psychological stress and stressrelated to trauma such as burns, surgery, shock, salicylate therapy andthe like.

The present invention encompasses these novel, oxaalkaonate zwitterioniccompounds, per se.

BACKGROUND ART

A wide variety of zwitterionic compounds are known in the literature andare generally disclosed as being useful as detergents. Of course, thecompounds of the present invention are also useful as detergents, butthey are notable among the alkyl zwitterionics by virtue of theiranti-ulcer activity.

Various alkyl zwitterionic compounds are disclosed in U.S. Pat. No.3,649,677, issued Mar. 14, 1972, to Peter Morris.

A variety of zwitterionic compounds are also disclosed in British Patentspecification No. 1,355,005, Bryan Anthony Brown, filed Feb. 9, 1972.

U.S. Pat. No. 2,697,659, issued Dec. 21, 1974, to Stayner and Stayner,discloses a variety of alkaryl zwitterionics.

Netherlands Pat. No. 7301766, bearing the terinzagelegging date Aug. 13,1973, discloses means for manufacturing an extremely wide variety ofalkyl and alkaryl zwitterionic compounds.

U.S. Pat. No. 3,544,501, issued Dec. 1, 1970, teaches the use of variouszwitterionic compounds for coating fibers.

U.S. Pat. No. 2,199,397, issued May 7, 1940, teaches various"pentavalent" nitrogen compounds which are said to be usefulsurface-active materials.

Phosphonio carboxylate zwitterionic compounds are described in U.S. Pat.No. 3,504,024, issued Mar. 31, 1970.

Substituted betaine compounds are described in U.S. Pat. No. 2,082,275,issued June 1, 1937.

Liquid detergent compositions containing ampholytic betaine-typedetergents are disclosed in U.S. Pat. No. 3,912,662, issued Oct. 14,1975.

German DT No. 2,000,028 describes the use of various zwitterionicnitrogen compounds in the production of fibrillated pulp sheets.

U.S. Pat. No. 3,922,341 teaches means for increasing blood oxygen levels(previously decreased by lung disease) by administering a carboxyzwitterionic compound.

Apart from the general literature relating to zwitterionic compounds perse, various long-chain materials have been suggested for use in thetreatment of gastric and duodenal ulcers: J5-2025-706 and J5-2025-711.These two Japanese patents relate, respectively, to polyunsaturatedlong-chain alcohols and polyunsaturated esters of long-chain alcohols.

The interaction of zwitterionic alkyl betaine surfactants withbiological membranes has been studied by Allen, et al., FEBS LETTERS,September 1975, 158. The authors conclude that the zwitterionics tested,at low concentrations and under mild conditions, can induce a highdegree of membrane dissociation together with considerable preservationof enzymic activity.

Lore and Luciana, Physiology and Behavior 18, 745-45 (1977) haveobserved that stress phenomena cause ulcers in rats in a laboratory testsituation and propose physiologic mechanisms to explain thisobservation.

DISCLOSURE OF INVENTION

The present invention encompasses anti-ulcer, surfactant-typeoxaalkanoate zwitterionic compounds of the general formula ##STR1##wherein at least one R group is a lipophilic substituent, and R¹ is anoxygen-interrupted hydrocarbylene substituent, said substituent R¹preferably having a chain length no greater than about 11 total atoms.

Ester salts of the formula (A) zwitterionics are also encompassed bythis invention. Such compounds are of the formula

    (R).sub.3 N.sup.⊕ R.sup.1 CO.sub.2 R.sup.2,X.sup.⊖(B)

wherein R² is a hydrocarbyl substituent, e.g., methyl, ethyl, propyl,etc., and X is a halogen ion, especially bromide. Such esters areincluded in the term "oxaalkanoate zwitterionic surfactant compound" asused herein.

The syntheses of various oxaalkanoate zwitterionic surfactant compoundsare described in detail, hereinafter.

As pointed out in the copending application of Laughlin and Fu, citedabove, various oxaalkanoate zwitterionic compounds wherein at least onelipophilic R group contains greater than about 10 or 12 carbon atomsexhibit desirable anti-ulcer activity. However, the compounds wherein Ris C₁₄ through about C₂₂, and wherein R¹ is (--CH₂ CH₂ O)₃ CH₂ --, areunexpectedly superior anti-ulcer agents.

Preferred oxaalkanoate zwitterionic anti-ulcer and detersive surfactantcompounds herein are of the formula ##STR2## or hydrolyzable cationicester salts thereof, per formula (B).

The formula (C) compounds are characterized by: R as a hydrocarbylmoiety greater than C₁₀, including C₁₁ and higher alkyl (preferred),alkenyl, alkynyl, alkaryl and aryalkyl substituents; R³ and R⁴ which maybe the same (preferred) or different hydrocarbyl moieties in the mannerof R, but preferably C₁₀, or smaller; and R¹ is an alkylene oxide moietywith a chain length no greater than about 11 total atoms, preferablyethylene oxide of the formula --(CH₂ CH₂ O)_(n) CH₂ CH₂ --, --(CH₂ CH₂O)_(n) CH₂ -- or propylene oxide, ##STR3## wherein the integer n is 1, 2or 3, or higher.

The most highly preferred zwitterionics of this invention are those offormula (C) (or the B ester form) wherein R is C₁₄ to about C₂₂ alkyl,especially about C₁₄ to about C₁₈ alkyl; R³ and R⁴ are each short chainalkyl, e.g., methyl, ethyl and propyl, and R¹ is, for example, --CH₂ CH₂--O--CH₂ -- or oligomers thereof, or --CH₂ CH₂ CH₂ --O--CH₂ --, oroligomers thereof.

The zwitterionic compounds herein can also have two of the shorter chainR groups (e.g., R³ and R⁴ in formula C) joined with one another aroundthe nitrogen atom to provide a homocyclic or heterocyclic ring, e.g.,piperidinio, morpholinio, and the like. Such compounds are alsoencompassed by the present invention.

It is to be understood that the oxaalkanoate zwitterionic compoundsdefined by the foregoing formulae all exhibit detersive action as wellas the desirable pharmacological activity disclosed herein. Some of thecompounds are more pharmacologically active than others and these arepreferred for drug use. The ammoniotrioxaundecanoate compounds (e.g.,the N,N-dimethylammoniotrioxaundecanoates abbreviated "ATOU") arereadily prepared, and are preferred anti-ulcer agents. The 5- and6-oxahexanoate compounds are rather unstable. The preparation of theseand other representative "oxainterrupted" zwitterionics is disclosedhereinafter.

BEST MODE

The following reaction sequence is convenient and is universallyapplicable for preparing the oxaalkanoate zwitterionic compoundsencompassed by the present invention. ##STR4##

Both organo bromides and iodides can be used in Step 1. Reaction of theorgano halide with the amine is carried out at reflux over a period ofseveral hours.

The amine materials used in Step 1 can be synthesized by art-disclosedprocesses. In general, sodium salts of alkanol amines (amino alkoxides)can be reacted with sodium chloroacetate to provide the carboxylterminal group. The carboxyl substituent is esterified (conveniently,methyl or ethyl ester) prior to reaction with the organo halide.Alternatively, alkanolamines are reacted with acrylonitrile and theresulting aminoalkoxypropionitriles converted to the correspondingaminoalkoxypropionate ester.

The hydrolysis of the quaternary ester (Step 2) can be performed under avariety of conditions giving rise to a wide range of yields and workupprocedures. By far the most efficient method, where applicable, is thatof ion-exchange chromatography. Thus, an aqueous or alcoholic solutionof quaternary ester is treated on an OH⁻ form anion exchange resin nearroom temperature. The exchange of halide for hydroxide and subsequenthydrolysis occur rapidly at or near room temperature. The desiredzwitterionic material is obtained essentially free of inorganic halides.This method represents a considerable improvement over alcoholichydrolysis under reflux in that fewer side reactions occur and formation(and removal) of inorganic halides is not involved in the reaction andproduct isolation.

The preparation of representative oxaalkanoate compounds and estersthereof of the type encompassed by this invention is described in thefollowing examples.

EXAMPLE I Preparation of n-C₂₂ H₄₅ N.sup.⊕ (CH₃)₂ CH₂ CH₂ OCH₂ CH₂CO₂.sup.⊖

3-(Dimethylaminoethoxy)-propionitrile prepared in the manner disclosedin Bull. Soc. Chim. Fr. 1960, 1162 (42.0 g) was hydrolyzed in thepresence of p-toluenesulfonic acid monohydrate (133.2 g) and absoluteethanol (16.1 g) for 15 hours at about 80° C. to produce, afterdistillation, the clear liquid ethyl 6-(dimethylamino)-4-oxahexanoateester.

Commercial docosylbromide (3.90 g) and the foregoing oxahexanoate ester(1.90 g) were heated to reflux in acetonitrile (8 hours) to yield anoff-white solid upon cooling and ether trituration. The isolated solidproduct was recrystallized from acetone to produce the quaternary ester,ethyl 6-docosyldimethylammonio-4-oxahexanoate bromide.

The foregoing quaternary ester bromide (24.0 g) was diluted in a 50:50methanol: H₂ O (75 ml) mixture and treated with sodium carbonate Na₂ CO₃(8.90 g) at 60° C. (3 hours). The reaction mixture was cooled (0° C.)and the inorganic ppt filtered. The resulting supernatant was passedthrough a mixed-bed resin (70 g; Rexyn 300 (H--OH)) and dried to producean off-white solid. This material was crystallized from CHCl₃ /acetoneto yield the title compound.

In like fashion are prepared the C₁₁, C₁₂, C₁₃, C₁₄, C₁₅, C₁₆, C₁₇, C₁₈,C₁₉, C₂₀, C₂₁, C₂₃, C₂₄, C₂₅, C₂₆, C₂₇, C₂₈, C₂₉ and C₃₀6-dimethylammonio-4-oxahexanoate compounds from the respective n-alkylbromides.

EXAMPLE II Preparation of n-C₁₄ H₂₉ N.sup.⊕ (CH₃)₂ (CH₂ CH₂ O)₃ CH₂CO₂.sup.⊖

Commercial Cl(CH₂ CH₂ O)₃ H (abb. ClE₃ H) (2.0 mole) and dimethylamine(20.0 mole) were mixed in a flask (3.0 l) fitted with a condenser andstirred (RT) for 30 hours. TLC (Si-gel) examination showed the completeconsumption of the ClE₃ H. Excess dimethylamine was removed by twoconsecutive evaporations under reduced pressure. The residual materialwas reconstituted in CHCl₃, dried (MgSO₄), filtered and evaporated todryness to produce the product, 8-dimethylamino-3,6-dioxaoctanol.

A warmed (50° C.) solution of 8-dimethylamino-3,6-dioxaoctanol (83.0 g)and NaH (26.9 g) in tetrahydrofuran under argon was treated with sodiumchloroacetate (58.5 g), by dropwise addition, and refluxed (12 hours).The cooled reaction mixture (RT) was diluted with acidic ethanol (H₂ SO₄-10%; 2.0 l), evaporated to dryness, reconstituted with ethanol andrefluxed (8 hours). The hot solution was then evaporated to a viscousoil and poured onto salt (NaCl 80 g) ice (400 g) and neutralized withconcentrated aqueous ammonia (pH 9.0). The final basic solution wasextracted with chloroform (3×30 ml) and dried (MgSO₄). The solution wasfiltered and evaporated to dryness to produce 72.0 g of ester. Thisliquid was distilled to yield ethyl11-dimethylamino-3,6,9-trioxaundecanoate as a clear liquid.

Tetradecylbromide (17.5 g) and ethyl11-dimethylamino-3,6,9-trioxaundecanoate ester (15.0 g) were heated (95°C.) overnight. The reaction mixture was titurated with ether andevaporated to dryness under vacuum (<1.0 mm Hg) for 12 hours.

The preceding quaternary ester bromide in ethanol (90%) was elutedsuccessively through a base-resin Rexyn 201 (HO⁻)) and mixed-bed resin(5.0 g; Rexyn 300 (HO.sup.⊖,H.sup.⊕)). Each column was eluted with asecond volume of ethanol to dislodge any weakly-bound product. Thesolution was filtered to remove extraneous resin; and evaporated todryness. The title compound was isolated as a viscous liquid.

In like manner are prepared the following alkyldimethyltrioxaundecanoate zwitterionic compounds from the respectivealkyl halides and ethyl 11-dimethylamino-3,6,9-trioxaundecanoate ester:the n-C₁₆ H₃₃ compound; the n-C₁₈ H₃₇ compound; the n-C₂₀ H₄₁ compound;the n-C₂₂ H₄₅ compound. The above-described synthesis scheme appears tobe appropriate for the manufacture of any of the alkylN,N-dimethylammoniotrioxaundecanoate compounds disclosed herein.Accordingly, in like fashion are prepared the corresponding n-alkyl C₁₀,C₁₁, C₁₂, C₁₃, C₁₅, C₁₇, C₁₉, C₂₁, C₂₃, C₂₄, C₂₅, C₂₆, C₂₇, C₂₈, C₂₉ andC₃₀ N,N-dimethylammoniotrioxaundecanoate compounds, and their esters.

EXAMPLE III Preparation of ##STR5##

Commercial N-2-hydroxyethylmorpholine (26.40 g), and sodiumchloroacetate (34.0 g) were heated (60° C.) under reduced pressure (5.0mm), treated with 50% NaOH (25.30 g) by dropwise addition and permittedto stand overnight. The reaction mixture was cooled to room temperatureand the viscous white residue was diluted with acidic ethanol (H₂ SO₄-ethanol; 25:100). A white residue was removed by filtration and thesolution refluxed (10 hours). The volatile solvents were removed underreduced pressure to produce a viscous solution which was poured ontosalted ice (NaCl-400 g), neutralized in NH₄ OH to pH 9.0 and extractedwith CHCl₃. The CHCl₃ solution was dried (MgSO₄), the solventevaporated, and the residue distilled to yield ethyl5-(N-morpholino)-3-oxapentanoate.

Docosyliodide (14.50 g) and ethyl 5-(N-morpholino)-3-oxapentanoate(14.50 g) were heated (165° C.) overnight to form at room temperature abrown solid which was recrystallized from acetone to yield the docosylmorpholinio quaternary ester iodide. The isolated quaternary (28 g) wasdissolved in 200 ml ethanol, diluted with K₂ CO₃.11/2H₂ O (14.20 g) andheated (80° C.) for 4 hours. The reaction mixture was cooled to RT,filtered, and eluted through mixed bed resin (100 g; Rexyn 300 (H-OH))to remove ionic impurities. Evaporation of the alcohol solution producedthe title compound.

EXAMPLE IV Preparation of C₂₂ H₄₅ N⁺ (CH₃)₂ CH₂ CH₂ CH₂ OCH₂ CO₂ ⁻

Ethyl-6(dimethylamino)3-oxahexanoate ester. Under argon,3-dimethylaminopropanol (103.20 g) was added dropwise to NaH (28,80 g)in dry tetrahydrofuran (THF) (0.30 l) and refluxed (4 hours). A slurryof dry sodium chloroacetate (163.10 g) in THF (0.20 l) was addedcarefully to the preceding mixture (RT) and refluxed (24 hours). Theresulting white resinous residue was neutralized with acidic ethanol(0.40 l; 5% vol. H₂ SO₄), evaporated to dryness under reduced pressureto remove traces of THF, further diluted with acidic ethanol (0.50 l;10% vol. H₂ So₄) and refluxed (8 hours). The cooled reaction mixture(RT) was filtered to remove white precipitate, evaporated to dryness,poured onto salted (NaCl: 100 g) ice and neutralized with NH₄ OH (pH9.0). The solution was extracted with CHCl₃ (3×0.30 l) and dried(MgSO₄). Subsequent filtration and solvent evaporation produced thedesired product as a liquid (137.0 g; 65.0%); bp=88° /2.70 mm.

Ethyl-6(dimethylamino)3-oxahexanoate ester (10.61 g; 0.050 mole) anddocosylbromide (18.30 g) were diluted with acetonitrile (0.025 l) andheated (95° C.) for 24 hours. The cooled reaction mixture produced asolid which crystallized from acetone to yield (23.90 g; 85%) as whitecrystals of ethyl 6(dimethyldocosylammonio)3-oxahexanoate bromide. Theproduct was examined by TLC (Silica Gel; CHCl₃ /MeOH/H₂ O 80:25:3.0) andfound to exhibit a single spot.

Ethyl 6(dimethyldocosylammonio)3-oxahexanoate bromide (12.0 g; 0.020mole) was dissolved in ethanol (0.04 l; 90%) and eluted through twosuccessive ion-exchange resin columns which contained base resin (72.0 gwet; Rexyn 201-HO) and mixed-bed resin (15.0 g wet; Rexyn 300-H-OH). Thecolumn eluant was evaporated to dryness and the residue crystallizedfrom CHCl₃ -hexane to produce white crystals (9.0 g) of the titlecompound.

In like fashion are prepared the C₁₁, C₁₂, C₁₃, C₁₄, C₁₅, C₁₆, C₁₇, C₁₈,C₁₉, C₂₀, C₂₁, C₂₃, C₂₄, C₂₅, C₂₆, C₂₇, C₂₈, C₂₉ and C₃₀6-dimethylammonio-3-oxahexanoate compounds from the correspondingn-alkyl bromides.

Industrial Applicability

Those aspects of this invention which relate to the use of the presentcompounds in ulcer therapy and/or prophylaxis comprise simplyadministering the oxaalkanoate compound orally to a patient in need ofsuch treatment. Any convenient oral dosage form can be used, and singledosages can range from about 18 mg to 2500 mg, and higher. Multipledosages can be administered daily, as needed. Optimally, theoxaalkanoate compound is administered prior to mealtimes, but foodprotein does not interfere with anti-ulcer activity.

Of course, the total daily usage of the compounds herein will be decidedby the attending physician. For example, the usage rate for theoxaalkanoate compositions will be determined by such factors as the typeof disease state being treated, the age and weight of the patient, theseverity of the condition, the length of time the patient will beundergoing therapy and like factors well known in the medical arts. Ingeneral, oral treatment regimens according to the present inventioncomprise orally administering to a human or lower animal in need of suchtreatment from about 10 mg/kg to about 3000 mg/kg (preferably 25mg/kg-500 mg/kg) per day of the zwitterionic compound, especially, theC₁₄ ATOU, C₁₆ ATOU, C₁₈ ATOU, C₂₀ ATOU, C₂₂ ATOU compounds, and theirrespective esters (the ethyl esters are convenient). (By "mg/kg" hereinis meant milligrams per kilogram of patient body weight; see AnimalTesting, hereinafter.)

For purposes of oral administration, the compounds of this invention canbe formulated as capsules, tablets, chewable tablets, powders, granules,solutions, suspensions, or the like. For treatment of non-human animals,the compounds are preferably incorporated in animal feeds, feedsupplements or feed concentrates.

The compounds of the present type are orally adinistered, preferably inunit dosage form in combination with excipients such as solid or liquidfillers, diluents or encapsulating substances which provide apharmaceutical carrier, e.g., materials commonly used in the manufactureof tablets, capsules, elixirs, and the like. Some examples of thesubstances which can serve as pharmaceutical carriers herein includesugars such as lactose, glucose and sucrose; starches such as cornstarch and potato starch; cellulose and its derivatives, such as sodiumcarboxymethylcellulose, ethylcellulose and cellulose acetate; powderedgums; malt; gelatin, stearic acid; calcium sulfate; vegetable oils, suchas peanut oil and cottonseed oil; mineral oil; polyols such as propyleneglycol, glycerin, sorbitol, mannitol and polyethylene glycol; agar;alginic acid; as well as other non-toxic, compatible substances used inpharmaceutical formulations. Wetting agents and lubricants, coloringagents, flavoring agents and preservatives can also be present. Entericcoatings can be used in standard fashion to provide prolonged release ofthe compositions and/or release in the intestines rather than in thestomach.

The compounds herein can optionally be co-administered orally with aneffective amount of an antacid. Aluminum hydroxide (hydrated alumina,available as Amphojel®, Aldrox®, etc.), magnesium oxide, magnesiumcarbonate, calcium carbonate, magnesium trisilicate, magnesiumhydroxide, and mixed magnesium/aluminum oxides and hydroxides, all ofwhich are well-known antacids used in the management of duodenal andgastric ulcers, can be incorporated in the compositions of the presentinvention at their common usage levels (generally 100-500 mg antacid perunit dose, although more or less can be used, according to the desiresof the formulator).

The compositions herein can be prepared by formulation and tabletingtechniques commonly used in the pharmaceutical industry.

Animal Testing

The oxaalkanoate compounds of this invention were tested for anti-ulceractivity in the Shay Rat Pylorus-Ligation Gastric Ulcer Test. Thedetails of the Shay Rat test system are found in general texts. The testindicates that optimal anti-ulcer activity for the oxaalkanoate is inthe range of about 25-500 mg/kg/day. While higher dosages can be used,dosages of up to about 100 mg/kg four times each day (before meals andat bedtime) are conveniently administered, orally.

As can be seen from the following data, representative oxaalkanoatecompounds of the present type are excellent anti-ulcer agents, both withregard to incidence and severity of ulcers.

    ______________________________________                                        ANIMAL TEST DATA                                                              Treatment         100 mg/kg                                                   ______________________________________                                        Ulcer Incidence (%) Test                                                      H.sub.2 O Control (avg.)                                                                        100%                                                        C.sub.14 ATOU     25%                                                         C.sub.22 ATOU     25%                                                         C.sub.14 ATOU ethyl ester                                                                       14%                                                         Ulcer Severity Test*                                                          H.sub.2 O Control 4.8                                                         C.sub.14 ATOU     1.8                                                         C.sub.22 ATOU     1.2                                                         C.sub.14 ATOU     1.1                                                         ______________________________________                                         *A reading of 1 in the severity grade indicates inflammation, but no          ulceration. Grades above 1 indicate ulceration.                          

The following examples further illustrate the practice of this inventionbut are not limiting thereof.

EXAMPLE V

    ______________________________________                                        Ingredient      mg. per capsule                                               ______________________________________                                        C.sub.14 ATOU   1000                                                          ______________________________________                                    

Four gelatin capsules of the above type are administered orally at threehour intervals four times daily to substantially reduce duodenalulceration in a human or animal in need of such treatment.

EXAMPLE VI

Tablets are prepared by conventional methods, as follows:

    ______________________________________                                        Ingredient       mg. per tablet                                               ______________________________________                                        C.sub.22 ATOU      500                                                        Starch             50                                                         Lactose            50                                                         Hydrated alumina*  100                                                        Magnesium stearate**                                                                             1.5                                                        ______________________________________                                         *Conventional antacid                                                         **Tableting aid and lubricant                                            

Two tablets of the above type are administered orally six times daily tosubstantially reduce the pain associated with duodenal ulceration.

In the tablets of Example VI, the hydrated alumina is replaced by anequivalent amount of magnesium oxide, magnesium carbonate, mixedmagnesium/aluminum oxides and hydroxides, calcium carbonate, magnesiumtrisilicate, and magnesium hydroxide, respectively, and equivalentresults are secured.

EXAMPLE VII

Standard pharmaceutical gelatin capsules containing 50 mg. of thecompounds of any of Examples I through IV herein, respectively, areprepared using conventional methods.

One 500 mg. gelatin capsule of any of the foregoing is administeredorally four times daily at regular intervals (preferably beforemealtimes and at bedtime) to reduce the incidence of ulceration of thegastrointestinal muscosal lining.

EXAMPLE VIII

In a modification of the capsules of Example VII, the Example I throughIV compounds are replaced by 500 mg. of their respective ethyl estersand equivalent results are secured.

EXAMPLE IX

Chewable tablets are prepared in the manner of Example VI comprising 250mg. of magnesium-aluminum hydroxide (hydrated magnesium aluminum oxide)and 250 mg. of any of the compounds of Examples I through IV herein, ortheir C₁ -C₅ esters. Two tablets are chewed and swallowed three timesdaily to reduce excess stomach acidity and to reduce stomach ulceration.

The detergency use of the present oxaalkanoate compounds is illustratedby the following. EXAMPLE X

A heavy-duty disinfectant/detergent composition especially useful forhard surface cleaning is as follows.

    ______________________________________                                        Ingredient             % (wt.)                                                ______________________________________                                        C.sub.16 ATOU          5.0                                                    Sodium C.sub.11-13 alkylbenzene sulfonate                                                            2.0                                                    Pluronic*              16.0                                                   Sodium carboxymethylcellulose                                                                        0.75                                                   Perfume and color      0.25                                                   Water                  Balance                                                ______________________________________                                         *Commercial mixture of detersive nonionic surfactants.                   

The composition of Example X is applied directly to floors, walls, etc.,in a standard cleaning operation to provide desirable cleansing anddisinfecting benefits.

What is claimed is:
 1. Compounds of the formula ##STR6## or ester saltthereof wherein R is an alkyl group containing from 11 to 30 carbonatoms; R³ and R⁴ are each methyl, ethyl or propyl; n is 2 or 3; m is 1,2 or 3; and p is 1 or
 2. 2. A compound according to claim 1 which is aC₁₄ to C₂₄ ammonio oxahexanoate, or ester salt thereof.
 3. A compoundaccording to claim 1 which is a C₁₄ to C₂₄ ammonio trioxaundecanoate, orester salt thereof.
 4. A compound according to claim 3 which is n-C₁₄H₂₉ N.sup.⊕ (CH₃)₂ (CH₂ CH₂ O)₃ CH₂ CO₂.sup.⊖, or ester salt thereof. 5.A compound according to claim 3 which is n-C₁₆ H₃₃ N.sup.⊕ (CH₃)₂ (CH₂CH₂ O)₃ CH₂ CO₂.sup.⊖, or ester salt thereof.
 6. A compound according toclaim 3 which is n-C₁₈ H₃₇ N.sup.⊕ (CH₃)₂ (CH₂ CH₂ O)₃ CH₂ CO₂.sup.⊖, orester salt thereof.
 7. A compound according to claim 3 which is n-C₂₀H₄₁ N.sup.⊕ (CH₃)₂ (CH₂ CH₂ O)₃ CH₂ CO₂.sup.⊖, or ester salt thereof. 8.A compound according to claim 3 which is n-C₂₂ H₄₅ N.sup.⊕ (CH₃)₂ (CH₂CH₂ O)₃ CH₂ CO₂.sup.⊖, or ester salt thereof.
 9. A compound according toclaim 3 which is n-C₂₄ H₄₉ N.sup.⊕ (CH₃)₂ (CH₂ CH₂ O)₃ CH₂ CO₂.sup.⊖, orester salt thereof.
 10. Compounds of the formula ##STR7## or ester saltthereof wherein R is an alkyl group containing from 11 to 30 carbonatoms.